Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety, and Gut Microbiome in Infants with Cow's Milk Protein Allergy

This open-label, non-randomized, multicenter trial (Registration: NCT 03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow's milk protein allergy (CMPA). Term infants aged 1-8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 20 -fucosyllactose (20-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from -0.31 at the baseline to +0.28 at the 4-months' follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.